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The science of manufacturing, at scale

With all eyes on scientific outcomes in the clinic, one of the less visible aspects of conducting human clinical trials for new drugs is fine-tuning the manufacturing process to ensure the product can be produced at scale and at sufficiently high, commercial quality.

Like most new pharmaceutical products, AMP945 was first discovered by scientists in a research lab, where new compounds are produced in small quantities, sufficient to sustain initial research activities. But as products move through clinical development, there is a need to scale production and generate larger volumes, which is a highly focused and calculated process.

With two Phase 2 clinical trials planned for AMP945, Amplia’s Director of Operations, Dr Rhiannon Jones, is working closely with offshore manufacturing facilities to oversee the production of AMP945 for the trial.

“This optimisation phase is important and it’s an iterative approach. At each stage, we need to be thinking about how manufacturing can be adapted to larger quantities, while remaining cost effective and safe,” said Rhiannon. 

While manufacturing AMP945, the active ingredient, is the first part of the process, producing a stable capsule that can deliver the drug at the correct dosage, can be as complex as producing the drug itself. Amplia has been working closely with a partner in the US to develop a drug formulation which will make AMP945 suitable for encapsulation. This is a multi-phase process, which requires several critical decisions along the way – from the contents of the capsule (including non-active ingredients that influence things like absorption and stability), through to the actual size of the capsule.

“This is where initial dosage studies are critical, informing how much active ingredient needs to be included in each capsule to administer the optimal treatment dose,” explained Rhiannon.

“Once we’ve determined the dose, we can start to make decisions about the strength of the capsules. This involves investigating how much AMP945, together with the non-active ingredients, we can physically get into a capsule, and balancing that against other factors, such as capsule size and cost. We want to be able to produce the most cost-effective product we can, but we also need to consider practical matters, such as how many capsules the patient will need to take each day - especially if they are taking AMP945 in combination with other treatments.

“The trial design will also be a consideration at this stage. If we’re running a double-blind study, we need to be able to produce identical capsules to deliver different dosages, as well as a placebo, as a measured point of comparison.”

All manufacturing is completed under GMP - Good Manufacturing Practice - to ensure that the final product is both unadulterated and made in a manner which is compliant with regulatory requirements. The final product is also tested for temperature stability, to ensure that it can be shipped and stored at the clinical trial sites without compromising the drug’s quality. 

With the Phase 2 clinical trial in pancreatic cancer patients soon due to commence, a shipment of capsules is now ready and waiting for the first patient to be enrolled in the trial. 

Rhiannon added that: “This is a major milestone for Amplia, but from a manufacturing perspective, we continue to look ahead to the next phase of development.

“We’re currently completing a five-kilogram manufacturing run of AMP945, but if this year’s clinical trials are successful, we’ll be working closely with our manufacturing partners to have plans in place to produce commercial quantities when they’re needed.”

With clinical activities set to ramp up, Amplia has further expanded its specialist team with the  appointment of Adrian Sulistio as CMC Project Manager to drive the manufacturing forward. 

Amplia’s CEO and Managing Director, John Lambert said: 

“Adrian joins the team with an impressive combination of experience and expertise in the clinical production process, and we are delighted to have him on board as we move into this critical phase of clinical development of AMP945.”